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A Study of Enzalutamide Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01288911
First Posted: February 3, 2011
Last Update Posted: September 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc
  Purpose
The purpose of this study is to determine the efficacy and safety of oral enzalutamide compared to bicalutamide in castrate men with metastatic prostate cancer who have progressed while on Luteinizing Hormone Receptor Hormone (LHRH) agonist/antagonist or after receiving a bilateral orchiectomy.

Condition Intervention Phase
Prostatic Neoplasms Drug: enzalutamide Drug: Bicalutamide Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment [ Time Frame: From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]

    PFS is the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by the ICR, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first.

    Radiographic disease progression was defined as either a progression in soft tissue on computed tomography (CT)/magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan.

    A skeletal-related event was any radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain.

    The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.



Secondary Outcome Measures:
  • PFS Based on Investigator Assessment [ Time Frame: From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]

    PFS was calculated as the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by investigators, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first.

    Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan.

    A skeletal-related event was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain.

    The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.


  • Prostate-specific Antigen (PSA) Response by Week 13 [ Time Frame: Baseline to Week 13 ]
    The PSA response by Week 13 was defined as the percentage change from Baseline to the smallest PSA value after Baseline (i.e., a decrease of 100% represents the largest possible decrease to a value below the lower limit of quantification) and on or before day 99 (i.e., upper boundary of the Week 13 visit window). For participants with no decrease in PSA post-baseline by Week 13, the PSA response by Week 13 was the smallest increase in PSA up to day 99. For participants with no post-baseline PSA values up to day 99, the PSA response by Week 13 was set to missing. PSA was analyzed at a central laboratory.

  • Best Prostate-specific Antigen (PSA) Response [ Time Frame: Baseline to the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]
    The best PSA response was defined as the percentage change from Baseline to the smallest PSA value after Baseline including PSA results from samples taken after the study drug was stopped. For participants with no decrease in PSA post-baseline, the best PSA response was the smallest increase in PSA. For participants with no post-baseline PSA values, the PSA response was set to missing. PSA was analyzed at a central laboratory.

  • Time to PSA Progression [ Time Frame: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]
    Time to PSA progression was calculated as the time interval from the date of randomization to the date of first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir (or above the baseline value for patients who did not have a decline in PSA post-baseline values), and confirmed by a second consecutive PSA assessment at least 3 weeks later. For participants with no documented PSA progression, the time to PSA progression was censored on the date the last PSA sample was taken.

  • Time to PSA ≤ 4 ng/mL [ Time Frame: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]
    Time to PSA ≤ 4 ng/mL was defined as the time interval from the date of randomization to the first date a decline in PSA to a result of 4 ng/mL or below was recorded. In participants without PSA results ≤ 4 ng/mL, the time to PSA ≤ 4 ng/mL was censored on the date of the last PSA sample taken. Participants with a PSA result ≤ 4 ng/mL at Baseline, participants with no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization

  • Time to ≥ 30% PSA Decline From Baseline [ Time Frame: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]
    The time to ≥ 30% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 30% was recorded. In participants without ≥ 30% PSA decline from Baseline, the time to ≥ 30% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization

  • Time to ≥ 50% PSA Decline From Baseline [ Time Frame: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]
    The time to ≥ 50% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 50% was recorded. In participants without ≥ 50% PSA decline from Baseline, the time to ≥ 50% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization

  • Time to ≥ 90% PSA Decline From Baseline [ Time Frame: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]
    The time to ≥ 90% PSA decline from Baseline was defined as the time interval from the date of randomization to the first date a PSA decline from Baseline of at least 90% was recorded. In participants without ≥ 90% PSA decline from Baseline, the time to ≥ 90% PSA decline from Baseline was censored on the date of the last PSA sample taken. Participants who had no Baseline PSA and participants with no post-baseline PSA results were censored on the date of randomization

  • Radiographic PFS Based on ICR Assessment [ Time Frame: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]

    Radiographic PFS was calculated as the time interval from the date of randomization to the first date of radiographic disease progression.

    Radiographic disease progression was defined as either a progression in soft tissue on CT/MRI scan according to RECIST 1.1, and/or a progression in bone lesions (a minimum of 2 new bone lesions as compared to previous scan) on bone scan and confirmed by the next bone scan.


  • Percentage of Participants With an Objective Response [ Time Frame: From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]

    Response assessments were reported by ICR for target lesions in soft tissues and non-target lesions in soft tissues based on CT and/or MRI according to RECIST version 1.1.

    Objective response was defined as the number of participants achieving either a complete response (CR) or a partial response (PR) based on participant's best overall response assessed at the end of the treatment.


  • Percentage of Participants With Adverse Events [ Time Frame: From initiation of study drug up to 30 days after the last dose of study drug or the 30-day safety follow-up visit, whichever occurred last. Median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm. ]

    A serious adverse event was defined as any untoward medical occurrence that at any dose:

    • Resulted in death
    • Was life threatening
    • Resulted in persistent or significant disability/incapacity
    • Resulted in congenital anomaly or birth defect
    • Required inpatient hospitalization or led to prolongation of hospitalization
    • Other medically important events.

    Treatment-related indicates adverse events assessed by the Investigator as probably or possibly related to study treatment.



Enrollment: 375
Actual Study Start Date: March 2, 2011
Estimated Study Completion Date: October 2017
Primary Completion Date: October 19, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide
Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
Drug: enzalutamide
capsules
Other Name: MDV3100
Active Comparator: Bicalutamide
Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
Drug: Bicalutamide
tablets
Other Name: Casodex

Detailed Description:
An open-label period has been added to the main protocol. Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over bicalutamide as assessed by the primary endpoint, all ongoing enzalutamide treated participants and ongoing or previous bicalutamide treated participants that meet entry criteria will be offered open-label enzalutamide at the discretion of the participant and study investigators.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
  • Ongoing androgen deprivation therapy with a Luteinizing Hormone Receptor Hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of randomization or bilateral orchiectomy (i.e., surgical or medical castration)
  • Metastatic disease documented by one of the following:

    • At least two bone lesions on bone scan, or
    • Soft tissue disease documented by computed tomography (CT)/ magnetic resonance imaging (MRI), or
    • Unequivocal pelvic adenopathy short axis > 2.0 cm in diameter by CT/MRI
  • Progressive disease at study entry defined as one or more of the following three criteria occurring in the setting of castrate levels of testosterone:

    • Prostate Specific Antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value should be ≥ 2 µg/L (2 ng/mL);
    • Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
    • Bone disease progression defined by two or more new lesions on bone scan
  • Asymptomatic or mildly symptomatic from prostate cancer (i.e. the score on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 must be < 4); no use of opiate analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior to randomization
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, including subjects with decreased performance status not attributed to progressive and symptomatic prostate cancer
  • Estimated life expectancy of ≥ 12 months
  • Able to swallow the study drug and comply with study requirements
  • A male subject and his female spouse/partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period, and for 3 months after final study drug administration. Two acceptable forms of birth control include:

    1. Condom (barrier method of contraception), AND
    2. In addition to a condom, one of the following acceptable forms of contraception is required:

      • Established use of oral, injected or implanted hormonal methods of contraception.
      • Placement of an intrauterine device (IUD) or intrauterine system (IUS).
      • Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
      • Tubal ligation for at least 6 months prior to Screening
      • Vasectomy or other surgical castration at least 6 months prior to Screening

Exclusion Criteria:

  • Prior cytotoxic chemotherapy for prostate cancer
  • Severe concurrent disease, infection, or comorbidity that would make the subject inappropriate for enrollment
  • Known or suspected brain and/or skull metastasis or active epidural disease
  • History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
  • Current or prior treatment with estrogens and/or drugs with anti-androgenic properties such as spironolactone > 50 mg/day, or progestational agents for the treatment of prostate cancer within 6 months prior to randomization
  • Current or prior use of ketoconazole for the treatment of prostate cancer
  • Use of antiandrogens within 6 weeks prior to randomization
  • Documented prior disease progression while receiving antiandrogens. Disease progression defined as PSA progression, radiographic progression and/or clinical deterioration.
  • Current or prior treatment with 5-α reductase inhibitors or anabolic steroids within 6 months prior to randomization
  • Prior use of systemic glucocorticoids (the equivalent of 10 mg of prednisone) within 3 months prior to randomization or expectation of their use during the study
  • Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to randomization
  • Major surgery within 2 months prior to randomization
  • History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization
  • Clinically significant cardiovascular disease including myocardial infarction within past six months or uncontrolled angina within past three months
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01288911


  Hide Study Locations
Locations
United States, Alabama
Site US1934
Homewood, Alabama, United States, 35209
United States, Alaska
Site US1527
Anchorage, Alaska, United States, 99503
United States, Arizona
Site US3026
Tucson, Arizona, United States, 85715
United States, California
Site US2977
Highland, California, United States, 92346
Site US3630
San Diego, California, United States, 92123
United States, Colorado
Site US2935
Denver, Colorado, United States, 80211
United States, Connecticut
Site US2945
Middlebury, Connecticut, United States, 06762
United States, Illinois
Site US2014
Melrose Park, Illinois, United States, 60160
Site US2067
Springfield, Illinois, United States, 62703
United States, Indiana
Site US2027
Jeffersonville, Indiana, United States, 47130
United States, Iowa
Site US1838
West Des Moines, Iowa, United States, 50266
United States, Kansas
Site US62
Kansas City, Kansas, United States, 66160-7233
United States, Maryland
Site US2976
Baltimore, Maryland, United States, 21201
Site US3182
Bethesda, Maryland, United States, 20889-5600
United States, Michigan
Site US2975
Ann Arbor, Michigan, United States, 48109
Site US892
Grand Rapids, Michigan, United States, 49546
United States, Minnesota
Site US20
Minneapolis, Minnesota, United States, 55455
United States, Montana
Site US3078
Billings, Montana, United States, 59101
United States, New Jersey
Site US2968
Lawrenceville, New Jersey, United States, 08648
United States, New York
Site US3025
Poughkeepsie, New York, United States, 12601
Site US1675
Rochester, New York, United States, 14642
Site US2934
Staten Island, New York, United States, 10304
United States, North Carolina
Site US81
Chapel Hill, North Carolina, United States, 27599
Site US2104
Greensboro, North Carolina, United States, 27403
United States, Ohio
Site US44
Cincinnati, Ohio, United States, 45267
Site US2185
Columbus, Ohio, United States, 43221
United States, Pennsylvania
Site US1598
Bala-Cynwyd, Pennsylvania, United States, 19004
Site US1680
Lancaster, Pennsylvania, United States, 17604
United States, South Carolina
Site US2926
Myrtle Beach, South Carolina, United States, 29572
United States, Tennessee
Site US1657
Nashville, Tennessee, United States, 37209
United States, Texas
Site US464
Houston, Texas, United States, 77030
Site US2978
San Antonio, Texas, United States, 78229
United States, Virginia
Site US1653
Virginia Beach, Virginia, United States, 23462
United States, Washington
Site US1580
Burien, Washington, United States, 98166
Site US1709
Wenatchee, Washington, United States, 98801
United States, Wisconsin
Site US51
Milwaukee, Wisconsin, United States, 53226
Belgium
Site BE3015
Brussels, Belgium, 1090
Site BE1322
Gent, Belgium, 9000
Site BE3018
Kortrijk, Belgium, 8500
Site BE3288
Leuven, Belgium, 3000
Site BE3289
Liege, Belgium
Site BE3013
Turnhout, Belgium, 2300
Canada, Alberta
Site CA3104
Calgary, Alberta, Canada, T2V 1P9
Canada, British Columbia
Site CA3242
Abbotsford, British Columbia, Canada, V2S 3N5
Canada, Ontario
Site CA2646
Kingston, Ontario, Canada, K7L 2V7
Site CA166
Toronto, Ontario, Canada, M4N 3M5
Site CA3084
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Site CA2984
Granby, Quebec, Canada, J2G 8Z9
Site CA170
Montreal, Quebec, Canada, H3G 1A4
Denmark
Site DK3354
Aalborg, Denmark, 9000
Site DK3356
Aarhus, Denmark, 8200
Site DK1857
Copenhagen, Denmark, 2200
Site DK1263
Herlev, Denmark, 2730
France
Site FR1091
Creteil, France, 94010
Site FR3009
Lille, France, 59037
Site FR442
Lyon Cedex 3, France, 69437
Site FR3002
Paris Cedex 10, France, 75020
Site FR3003
Poitiers Cedex, France, 86000
Site FR3000
Rennes Cedex, France, 35033
Site FR3007
Rouen, France, 76031
Site FR3005
Suresnes Cedex, France, 92151
Germany
Site DE4000
Nuertingen, Baden-Wuerttemberg, Germany, 72622
Site DE2989
Aachen, Germany, 51074
Site DE3287
Bergisch Gladbach, Germany, D-51465
Site DE2993
Bonn, Germany, 53105
Site DE2995
Bonn, Germany, 53111
Site DE2994
Bonn, Germany, 53117
Site DE2990
Hamburg, Germany, 22081
Site DE3270
Hannover, Germany, 30625
Site DE2992
Reutlingen, Germany, 72764
Site DE3286
Waldshut-Tiengen, Germany, 29761
Site DE2988
Wuppertal, Germany, 42103
Romania
Site RO3042
Bucharest, RO, Romania, 022328
Site RO3039
Bucharest, RO, Romania, 050659
Site RO3035
Bucharest, Romania, 041345
United Kingdom
Site GB3029
Bristol, UK, United Kingdom, BS2 8HW
Site GB3027
London, UK, United Kingdom, SE19RT
Site GB3030
London, UK, United Kingdom, SW17 0QT
Site GB3028
Cardiff, Wales, United Kingdom, CF14 4XW
Site GB3244
Belfast, United Kingdom, BT9 7AB
Site GB2702
Cambridge, United Kingdom, CB2 0QQ
Site GB3166
Glasgow, United Kingdom, G12 0YN
Site GB1862
Leicher, United Kingdom, LE5 4PW
Site GB3163
London, United Kingdom, NW1 2PG
Site GB2624
Manchester, United Kingdom, M20 4BX
Site GB3355
Merseyside, United Kingdom, CH63 4JY
Site GB3245
Northwood, Middlesex, United Kingdom, HA6 2RN
Site GB3290
Preston, United Kingdom, PR2 9HT
Sponsors and Collaborators
Astellas Pharma Inc
Medivation, Inc.
Investigators
Principal Investigator: Principal Investigator Carolina Urologic Research Center
Study Director: Associate Medical Science Director Astellas Pharma Global Development
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01288911     History of Changes
Other Study ID Numbers: 9785-CL-0222
2010-021868-15 ( EudraCT Number )
First Submitted: February 1, 2011
First Posted: February 3, 2011
Results First Submitted: October 15, 2015
Results First Posted: December 3, 2015
Last Update Posted: September 19, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc:
Metastatic
MDV3100
Prostate
progressive
Cancer
enzalutamide

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Bicalutamide
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents